Download Research Summary 2005-2006

Poxvirus and vaccines
Molecular and Cellular Biology
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Research summary
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The main objectives of our laboratory are
geared to understand molecular basis in
the pathogenesis of infectious agents
and their interaction with the host cell, as
well as to use this knowledge in the
development of vaccines that might be
effective against viral (HIV, hepatitis C)
and parasitic diseases (malaria and leishmaniasis), using vaccinia virus as a
model vector system.
In the period 2005-2006 we have made
the following observations.
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1) Defined the structure of one of the
more complex virus, Intracellular Mature
Vaccinia Virus (IMV) at the resolution between 4 and 6 nm, using cryomicroscopy
and electron tomographic reconstruction
(Cyrklaff, M et al 2005).
2) Identified Wiskott-Aldrich Syndrome
protein as needed for vaccinia virus
pathogenesis (Guerra et al, 2005).
3) Explained how alphaviruses, like
Sindbis (SV) and Semliki Forest virus (SFV),
escape the interferon-induced ds-RNA
dependent protein kinase (PKR) inhibitory
antiviral effects by a novel mechanism
that overpasses the requirement for eIF2
(Ventoso et al, 2006), identified ATF-3 as
a novel PKR-induced molecule that triggers apoptosis (Guerra et al, 2006), identified the tumor supresor ARF as antiviral
by promoting PKR release from its binding
to nucleophosmin (Garcia, M et al, 2006);
we also wrote a review on the impact of
PKR in celll biology (García et al, 2006).
4) Developed potential vaccines against
leishmaniasis (Pérez-Jiménez et al, 2005)
and against HIV/AIDS (Gómez et al,
2006a, 2006b).
5) As a result of our findings, three patent
applications have been submitted.
Figure 1: Mode of action of the protein
kinase PKR, an antiviral and antiproliferative regulator.
Selected publications
Cyrklaff, M., Risco, C., Fernández, J. J., Jiménez, M.V., Esteban, M., Baumeister, W. and
Carrascosa, J.L. (2005). Cryo-Electron tomography of vaccinia virus. Proc. Natl. Acad. Sci. USA.
102, 2772-2777.
Research summary
Publications
Personnel
Ventoso, I., Sanz, M. A., Molina, S., Berlanga, J. J., Carrasco, L. and Esteban, M. (2006).
Translational resistance of late alphavirus mRNA to eIF-2 alfa phosphorylation: a strategy
to overcome the antiviral effect of protein kinase PKR. Genes Development 20, 87-100.
Guerra, S., López-Fernández, L. A., García, M. A., Zaballos, A. and Esteban, M. (2006). Human
gene profiling in response to active protein kinase PKR in infected cells: involvement of the
transcription factor ATF-3 in PKR-induced apoptosis. J. Biol. Chem 281, 18734-18745.
García, M. A., Gil, J.,Ventoso, I., Guerra, S., Domínguez, E., Rivas, C. and Esteban, M. (2006).
The impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action.
Microb. Mol. Biol. Reviews 70, 1032-1060.
Garcia, M. A., Collado, M., Muñoz, C., Mathew, A., Arroyo, J., Esteban, M., Serrano, M. and Rivas,
C. (2005). Antiviral action of tumour suppressor ARF. The EMBO Journal 25, 4284-4292.
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Molecular and Cellular Biology
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Molecular and Cellular Biology
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Group Leader:
Mariano Esteban
Research summary
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Associated Scientists:
Alberto Ramos
Alejandro Piris
Postdoctoral Researchers:
Susana Guerra
Carmen E. Gómez
Jose Manuel González
Paul Heinen
Mariang García
Beatriz Perdiguero
Juan F. García
Predoctoral Researchers:
Elena Domingo
José Luis Nájera
Eva Pérez Jiménez
Magdalena Krupa
Jacobo Nieto
Ana Cáceres
Lucas Sánchez
Technical Assistants:
María Victoria Jiménez